Leveraging Single-Cell RNA-seq Data to Uncover the Association Between Cell Type and Chronic Liver Diseases

Components of liver microenvironment is complex, which makes it difficult to clarify pathogenesis of chronic liver diseases (CLD). Genome-wide association studies (GWASs) have greatly revealed the role of host genetic background in CLD pathogenesis and prognosis, while single-cell RNA sequencing (scRNA-seq) enables interrogation of the cellular diversity and function of liver tissue at unprecedented resolution. Here, we made integrative analysis on the GWAS and scRNA-seq data of CLD to uncover CLD-related cell types and provide clues for understanding on the pathogenesis.

We downloaded three GWAS summary data and three scRNA-seq data on CLD. After defining the cell types for each scRNA-seq data, we used RolyPoly and LDSC-cts to integrate the GWAS and scRNA-seq. In addition, we analyzed one scRNA-seq data without association to CLD to validate the specificity of our findings.

After processing the scRNA-seq data, we obtain about 19,002-32,200 cells and identified 10-17 cell types. For the HCC analysis, we identified the association between B cell and HCC in two datasets. RolyPoly also identified the association, when we integrated the two scRNA-seq datasets. In addition, we also identified natural killer (NK) cell as HCC-associated cell type in one dataset. In specificity analysis, we identified no significant cell type associated with HCC. As for the cirrhosis analysis, we obtained no significant related cell type.

In this integrative analysis, we identified B cell and NK cell as HCC-related cell type. More attention and verification should be paid to them in future research.